Glaucoma is a disease that affects millions of people worldwide, and for which there is no cure. The major focus of current strategies for glaucoma management is to preserve the vision that remains at the time of diagnosis. In afflicted eyes, retinal ganglion cells (RGCs) are lost, leading to an irrevocable loss of visual function. However, with the discovery of neural stem cells (NSCs), and with the finding that stem cells exist in the ciliary margin of the adult retina, the promise of RGC rescue/replacement, along with recovery of visual function, has becoming increasingly real. The ultimate goal of the work outlined here is intended to help develop a clinical means of restoring normal vision in human glaucoma patients. Using rodent models of glaucoma and RGC apoptosis (the type of cell death seen in glaucoma), we propose a multi-pronged approach that employs NSCs to rescue and replace sick or dead RGCs; we will also use axogenic factors in combination with NSCs to stimulate axon extension from the rescued or replaced neurons. Our pilot observations suggest that one of the NSC lines that we have used may provide trophic support to dying RGCs -these cells will be applied towards rescuing RGCs whose axons have been damaged. A second cell line has reportedly been used successfully to replace damaged retinal neurons (including RGCs) in dystrophic and mechanically damaged eyes; our aim is to use this second type of NSC to replace RGCs in glaucomatous eyes. In addition, specific neurite growth-inducing molecules or surgical manipulations that we have found to induce fiber extension, will be used to stimulate long distance axon projections from replaced RGCs. These experiments will be complemented with similar studies using stem cells harvested from the retina itself. The proposed studies will reveal the potential for using NSCs and axon-growth promoting molecules to reverse loss of vision in glaucomatous eyes.